A significant proportion of manic patients either do not respond adequately to conventional treatment (lithium with or without neuroleptics), or cannot tolerate the adverse effects associated with therapeutic doses of these agents. Anticonvulsants are a frequently utilized second-choice treatment, but are ineffective in one third or more of patients. Thus, a need exists for additional effective treatments. Reports in the literature suggest that calcium channel blocking agents may also have antimanic actions. This is consistent with the notion that lithium, the prototypical antimanic drug, exerts its therapeutic action by attenuation of a receptor-mediated rise of intracellular calcium. However, the efficacy of calcium channel blockers as an alternative therapy in treatment-resistant mania has never been subjected to definitive study with adequate numbers of subjects. Thus, we propose to conduct the largest (to our knowledge) controlled trial to date, of the calcium channel blocker verapamil, in bipolar manic patients who were unresponsive to four weeks of initial treatment with lithium. Medication will be administered under double-blind, random assignment conditions. A group assigned to continued-lithium administration will serve as a control for possible confounding effects due to stage of illness, insufficient duration of initial treatment, or spontaneous cycling out of mania. The specific aim of this investigation is to assess the acute treatment efficacy of verapamil for treatment-resistant mania. Based on this aim we will pursue two primary hypotheses: 1) the proportion of manic subjects who respond to acute treatment with verapamil will be significantly greater than the proportion who respond to continued-lithium treatment; and 2) the mean change in Bech-Rafaelsen mania ratings produced during verapamil treatment will be significantly greater than the corresponding change produced during continued-lithium treatment. We will also pursue a secondary hypothesis: 3) the need for adjunctive lorazepam (administered on a prn basis) will be greater in the continued-lithium group as compared to the verapamil group. Eighty eight subjects (two groups of 44 each) will be randomly assigned to treatment with verapamil or continued-lithium for four weeks. We anticipate that a maximum of 20% of patients will be withdrawn from the acute phase of the study due to reasons such as intolerable adverse effects or withdrawal of consent. Thus, we expect the entered sample to yield 35 completed subjects per cell. This sample size will allow for adequate statistical power to test the hypotheses stated above.